4-Demethoxydaunorubicin is an anthracycline derivative known to have antitumor activity as reported by F. Arcamone et al in Cancer Treatment Reports, Vol. 60(7), pages 829-834 (1976). Doxorubicin and daunomycin are closely related compounds of established clinical utility. Doxorubicin hydrochloride, available from Adria Laboratories Inc. under the trade name Adriamycin.RTM., has been approved by the Food and Drug Administration for use in clinical research, and is one of the most powerful anticancer drugs available.
At present, doxorubicin is produced commercially from a soil fungus by a fermentation process. A suitable fermentation technique for preparing doxorubicin is described in U.S. Pat. No. 3,590,028. Such techniques are inherently expensive and limit the types of molecules that can be produced. Because of the inherent disadvantages of presently available commercial techniques for producing doxorubicin and related compounds, substantial effort has been devoted to developing processes for producing such compounds by chemical synthesis.
Several syntheses of 4-demethoxydaunomycinone have been described in the literature. See, for example, Wong et al, Can. J. Chem., Vol. 49, p. 2412 (1971); Arcamone et al, British Pat. No. 2,601,785 (1975); Suzuki et al, Tetrahedron Letters 1977 p. 2303; Kerdesky et al, J. American Chem. Soc., 100(11), p. 3635 (1978); Kende et al, Tetrahedron Letters, 1977, p. 3537; and Jackson et al, J. American Chem. Soc. 101, p. 3989 (1979). Unfortunately, all of the above syntheses suffer short-comings that limit their practical utility.